Five undescribed monoterpene-chalcone conjugates (1-5), one undescribed hypothetical precursor of diarylheptanoid (6), two undescribed diarylheptanoids (7–8), and fourteen known compounds (9–22) were ...isolated from the seeds of Alpinia katsumadai. Their structures were elucidated through the interpretation of HRESIMS, NMR, ECD, and X-ray diffraction data. MTT assays on human cancer cell lines (HepG2, A549, SGC7901, and SW480) revealed that compounds 3–8, 11, and 13 exhibited broad-spectrum antiproliferative activities with IC50 values ranging from 3.59 to 21.78 μM. B cell lymphoma 2 was predicted as the target of sumadain C (11) by network pharmacology and verified by homogeneous time-resolved fluorescence assay and molecular docking.
Eight un\described compounds were isolated from the seeds of Alpinia katsumadai. BCL-2 was predicted as the possible target of compound 11 against HepG2 by network pharmacology and tentatively verified by HTRF assay and molecular docking. Display omitted
•Eight undescribed compounds were isolated from the seeds of Alpinia katsumadai.•Sumadain C (11) exhibited the most potent cytotoxicity against HepG2.•BCL-2 was tentatively verified as the target of sumadain C against HepG2.•Biosynthetic routes of the main compounds isolated herein were proposed.
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•16 New diarylheptanoid-chalcone hybrids were isolated from A. katsumadai.•Compounds 1–3, 5–7, 11–14, 21–25, and 27 showed PTP1B selective inhibition.•All compounds showed obvious ...inhibition on α-glucosidase.•Compounds 1, 3, and 12 were α-glucosidase and PTP1B mixed-type inhibitors.
The EtOH extracts of the dried seeds of Alpinia katsumadai were revealed with hypoglycemic effects on db/db mice at the concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 16 new diarylheptanoid-chalcone hybrids, katsumadainols A1−A16 (1–16), together with 13 known analogues (17–29), were isolated from A. katsumadai under the guidance of bioassay. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which compounds 1–3, 5–7, 11–14, 21–25, and 27 showed PTP1B/TCPTP selective inhibition with IC50 values ranging from 22.0 to 96.7 μM, which were 2–10 times more active than sodium orthovanadate (IC50, 215.7 μM). All compounds exhibited obvious inhibition against α-glucosidase with IC50 values of 2.9–29.5 μM, indicating 6–59 times more active than acarbose (IC50, 170.9 μM). Study of enzyme kinetics indicated compounds 1, 3, and 12 were PTP1B and α-glucosidase mixed-type inhibitors with Ki values of 13.1, 12.9, 21.6 μM, and 4.9, 7.4, 3.4 μM, respectively.
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•Ten new diarylheptanoid dimers were isolated from A. katsumadai.•Compounds 1–5 and 7–10 significantly stimulated GLP-1 secretion.•Compounds 1–4 showed obvious inhibition on ...GPa.•Compounds 1–5 and 10 were PTP1B selective inhibitors.•Compounds 1–4 were GLP-1 secretagogues and multiple-enzyme inhibitors.
Ten new diarylheptanoid dimers, katsumadainols C1 − C10 (1–10), were isolated from the seeds of Alpinia katsumada and elucidated by extensive spectroscopic methods, ECD calculations, and single-crystal X-ray diffraction. Their antidiabetic effects were evaluated by the stimulation of GLP-1 secretion in STC-1 cells and inhibition against four diabetes-related enzymes, GPa, α-glucosidase, PTP1B, and DPP4. Compounds 1–5 and 7–10 significantly stimulated GLP-1 secretion by 267.5–433.1% (25.0 μM) and 117.8–348.2% (12.5 μM). Compounds 1–4 exhibited significant inhibition on GPa with IC50 values of 18.0–31.3 μM; compounds 1–5 showed obvious inhibition on α-glucosidase with IC50 values of 6.9–18.2 μM; compounds 1–5 and 10 possessed PTP1B inhibitory activity with IC50 values ranging from 35.5 to 80.1 μM. This investigation first disclosed compounds 1–4 as intriguing GLP-1 secretagogues and GPa, α-glucosidase, and PTP1B inhibitors, which provided valuable clues for searching multiple-target antidiabetic candidates from Zingiberaceae plants.
Main observation and conclusion
The EtOAc fraction of Alpinia katsumadai seeds showed significant inhibition on glycogen phosphorylase a (GPa) with inhibitory ratios of 97.9% and 64.6% at ...concentrations of 200 and 100 μg/mL, respectively. Bioactivity‐guided isolation afforded 15 new diarylheptanoid‐flavanone hybrids, katsumadainols B1—B15 (1—15), together with eight known ones (16—23). Compounds 4—10 and 12—21 exhibited activity against GPa with IC50 values of 10.1—95.4 μmol/L; compounds 4, 5, 16, and 17 displayed inhibitory effects on α‐glucosidase with IC50 values of 7.1, 12.4, 7.2, and 8.3 μmol/L, obviously higher than acarbose (IC50, 209.1 μmol/L); compounds 4—6, 14, 16—20, 22, and 23 were PTP1B/TCPTP selective inhibitors with IC50 values of 40.7—95.8 μmol/L; compounds 4, 5, 16, and 17 showed DPP4 inhibitory effects with inhibitory ratios of 50.0%—54.2% (200 μmol/L). Diarylheptanoid‐flavanone hybrids (4, 5, 16, and 17) with a p‐hydroxybenzyl at C‐6 position represent a promising class of multiple‐target antidiabetic agents inhibiting GPa, α‐glucosidase, PTP1B, and DPP4.
Fifteen new diarylheptanoid‐flavanone hybrids, katsumadainols B1—B15 (1—15), along with eight known ones (16—23), were isolated from the seeds of Alpinia katsumadai. Compounds 4, 5, 16, and 17 represented a promising class of multiple‐target antidiabetic agents inhibiting GPa, α‐glucosidase, PTP1B, and DPP4.
•Five well recognized TCM plant species in the Zingiberaceae family were investigated.•External morphology characteristics were provided.•Volatile marker compounds from each species were identified ...using a SPME GC/Q-ToF method.•Characterization and quantification of triglycerides were achieved using a SFC/MS method.•Comprehensive profiles and quality standards were established for distinguishing between different species.
Volatile compounds (VCs) and triglycerides (TGs) are the primary groups of constituents in the fruits of five well-known species used in traditional Chinese medicine (TCM), viz. Alpinia oxyphylla Miq. (AO), Alpinia katsumadai Hayata (AK), Amomum villosum Lour. (FAL), Amomum villosum Lour. var. xanthioides T. L. Wu et Senjen (FALX), and Amomum longiligulare T. L. Wu (FALO). The fruits of these species are morphologically similar and commonly used in both foods and TCM. Each species is purportedly endowed with different medicinal properties. Efficient and environmentally friendly methods are desirable for the quality control of these species. The current study attempted to establish both comprehensive profiles and quality standards for the five TCM species. External morphology characters were provided to distinguish 18 fruit samples belonging to the five species, which were collected from different geographical regions of China. The VCs of each sample were analyzed by SPME GC/Q-ToF. The identification of marker compounds from each species allowed for the differentiation of the fruits from the five plants. Characterization and quantification of 21 TGs were achieved using SFC/MS with an analysis time of less than 15 min. The complex TGs were unambiguously identified using the MS detection with correct attribution of the acyl group to the sn-2 position. Moreover, the quantification of TGs was improved by using reference standards whenever possible or a single standard strategy to determine multiple TGs. The validity of the proposed SFC/MS method was assessed by analyzing fatty acids from the hydrolysis and transesterification products of the same sample set using GC/MS. The quantification results from both TGs and fatty acids were consistent, and were further substantiated by chemometric analysis. To our knowledge, this is the first comprehensive study utilizing the morphology, VCs, and TGs for quality evaluation purpose of these five TCM species.
Cardamonin is a chalcone that presents at high content in the seeds of Alpinia katsumadai Hayata. In recent decades, researchers have found that it is not only an edible spice, but also a remarkable ...herb with a wide range of pharmacological properties. However, its specific metabolic routes in vivo remain unclear while these metabolites may accumulate to exert pharmacological effects. Our study aimed to clarify the metabolic pathways of cardamonin after oral administration to rats. Here, an advanced UHPLC-Q-Exactive Orbitrap MS analytical technique was applied for efficient detection of metabolites in vivo, which especially showed benefits in obtainment of the fragment ions with relatively lower contents. We also established a novel strategy to identify metabolites based on typical fragmentation routes. The results indicated that a total of 40 metabolites could be categorized into 3 types with consideration of the particular structures and characteristic fragment ions. Then, diagnostic product ions (DPIs) of each type were summarized for further screening and identification of metabolites derived from cardamonin. Finally, methylation, demethylation, hydrogenation, hydroxylation, dehydroxylation, glucuronidation and sulfation were confirmed to be the major metabolic pathways in vivo. Our observation extended the metabolic mechanism of cardamonin and could be of great benefits to interpreting the action mechanism of cardamonin in vivo.
•The novel larvicidal compound was identified from Alpinia katsumadai.•The active compound was isolated by bioassay-guidance with some chromatography.•The active compound was elucidated by ...spectroscopic analysis with 1H NMR, 13C NMR, and ESI–MS.•The active compound was screening by foam cell formation test with THP-1 cells.•The active compound has larvicidal effect against Plutella xylostella L. and Mythimna separate.
Plutella xylostella and Mythimna separata are destructive insect pests causing damages to agricultural products. In this study, a larvicidal compound was identified by bioassay-guided isolation of methanol extracts of Alpinia katsumadai Hayata, a plant belonging to the Zingiberaceae, against P. xylostella and M. separata larvae. Because many insects, including P. xylostella and M. separate larvae, cannot synthesize sterols, they use phytosterols by converting them to the sterols necessary for hormonopoiesis, and resulting normal development, growth and reproduction. Results of our oil droplet formation test showed that compound 1 inhibited foam cell formation in ox-LDL treated THP-1 cells, suggesting that this compound may be inhibiting the sterol transport in insects. The compound 1 with larvicidal activity was elucidated by spectroscopic analysis (1H NMR, 13C NMR, and ESI–MS) as 2,3,22,23-tertrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18- tetracosatetraene. The 50% lethal concentration (LC50) values of compound 1 were 2μg/mL and 16.9μg/mL, respectively, against P. xylostella and M. separata larvae.
(E)-methyl-cinnamate (EMC), a phytochemical constituent isolated from
Hayata, is a natural flavor compound with anti-inflammatory properties, which is widely used in the food and commodity industry. ...However, the pharmacological effects of methyl-cinnamate on pre-osteoblasts remain unknown. This study aimed to investigate the pharmacological effects and mechanisms of EMC in pre-osteoblast MC3T3-E1 cells (pre-osteoblasts).
Cell viability and apoptosis were evaluated using the MTT assay and TUNEL staining. Cell migration and osteoblast differentiation were examined using migration assays, as well as alkaline phosphatase activity and staining assays. Western blot analysis was used to examine intracellular signaling pathways and apoptotic proteins.
EMC decreased cell viability with morphological changes and increased apoptosis in pre-osteoblasts. EMC also induced the cleavage of Poly (ADP-ribose) polymerase (PARP) and caspase-3 and reduced the expression of anti-apoptotic proteins. In addition, EMC increased TUNEL-positive cells in pre-osteoblasts, decreased the activation of mitogen-activated protein kinases, and suppressed cell migration rate in pre-osteoblasts. Subsequently, EMC inhibited the osteoblast differentiation of pre-osteoblasts, as assessed by alkaline phosphatase staining and activity assays.
These findings demonstrate that EMC has a pharmacological and biological role in cell survival, migration, and osteoblast differentiation. It suggests that EMC might be a potential phytomedicine for treating abnormalities of osteoblast function in bone diseases.
A natural chalcone, cardamonin (2',4'-dihydroxy-6'-methoxychalcone; CDN) was isolated from the seeds of
Hayata, which has been traditionally used to treat stomach aches. CDN has been reported to ...possess various pharmacological properties, including anticancer and anti-inflammatory effects. This study evaluated the antiviral activity of CDN against human coronavirus HCoV-OC43 and determined the mode of action in HCoV-OC43-infected human lung cell lines (MRC-5 and A549 cells). CDN significantly inhibited HCoV-OC43-induced cytopathic effects with an IC
of 3.62 μM and a CC
of >50 μM, resulting in a selectivity index of >13.81. CDN treatment reduced the level of viral RNA and the expression of spike and nucleocapsid proteins in HCoV-OC43-infected cells as determine through qRT-PCR and Western blot analysis. Additionally, the activation of p38 mitogen-activated protein kinase (MAPK) by anisomycin decreased viral protein expression, whereas an inhibitor of p38 MAPK signaling, SB202190, increased viral protein expression. CDN also amplified and extended the p38 MAPK signaling pathway in HCoV-OC43-infected cells. In conclusion, CDN inhibited HCoV-OC43 infection by activating the p38 MAPK signaling pathway and has potential as a therapeutic agent against human coronavirus.
To detect the effects of active compounds of Caodoukou () (ACAK) on the proliferation, migration and invasion of pancreatic cancer, and explain the possible molecular mechanism of ACAK interacting ...with these processes.
Cell counting kit-8 method, cell scratch repair experiment, Transwell migration and invasion experiment, immunohistochemistry, western blot assay and real-time polymerase chain reaction experiment were used to evaluate the effect of ACAK on the proliferation, migration and invasion of pancreatic cancer cells. The levels of active molecules involved in the phosphoinosmde-3-kinase (PI3K)/Akt/the mammalian target of rapamycin (mTOR) signal transduction were detected by Western blot assay. In addition, the function of ACAK was evaluated by xenotransplantation tumor model in nude mice.
The inhibitory effect of ACAK on the proliferation of pancreatic cancer cells showed certain time-dose dependence. The results of scratch repair test, Transwell test, Western blotting and real time polymerase chain reaction assay showed that ACAK could inhibit the migration and invasion of pancreatic cancer cells . In addition, the regulatory effect of ACAK on epithelial-mesenchymal transition (EMT) is partly attributed to PI3K/Akt/mTOR signaling pathway. The experimental results showed that ACAK regulated the development of pancreatic cancer.
ACAK can partly inhibit the activity of EMT and matrix metallopeptidases by down-regulating the downstream proteins of PI3K/Akt/mTOR signal pathway, thus inhibiting the ability of migration and invasion of pancreatic cancer.
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